Pharmacokinetics of propofol infusions, either alone or with ketamine, in sheep premedicated with acepromazine and papaveretum

The pharmacokinetics of propofol were investigated in two groups of five Scottish blackface sheep undergoing surgery for the implantation of subcutaneous tissue pouches. After premedication with acepromazine and papaveretum, anaesthesia was induced with either propofol at 4 mg kg⁻¹ intravenously (group 1) or with a mixture of propofol at 3 mg kg⁻¹ and ketamine at 1 mg kg ⁻¹ intravenously (group 2). Anaesthesia was maintained with a variable infusion rate of either propofol alone (group 1) or propofol and ketamine (group 2). Both regimens produced satisfactory conditions for superficial surgery of the body surface. The mean (SD) duration of anaesthesia was 64·8 (3·1) minutes for group 1 and 60 (0) minutes for group 2; the mean total dose of propofol given to the sheep in group 1 was 801 (84) mg, and the sheep in group 2 received 470 (46) mg of propofol and 267 (30) mg of ketamine. The mean elimination half-life of propofol was 56·6 (13·1) minutes in group 1 and 50·3 (21·4) minutes in group 2; the mean volume of distribution at steady state was 1037 (0480) litre kg⁻¹ in group 1 and 1·515 (0939) litre kg⁻¹ in group 2; the mean body clearance was 85·4 (28·0) ml kg⁻¹ min⁻¹ in group 1 and 1280 (35·0) ml kg⁻¹ min⁻¹ in group 2; the mean residence time corrected for a bolus injection was 12·1 (4·2) minutes in group 1 and 11·9 (6·6) minutes in group 2; for the infusion, the mean residence time was 72·1 (4·2) minutes in group 1 and 69·9 (7·9) minutes in group 2. There were wide variations in the blood propofol concentrations reached in individual sheep by using this standard dosing regimen. All the sheep recovered quickly from anaesthesia; the mean times to extubation, sternal recumbency and standing for the animals in group 1 were 2·8 (0·4) 6·3 (1·2) and 10·9 (1·6) minutes from the end of the infusion, and the times for group 2 were 5·3 (0·9), 11·2 (1·7) and 15·1 (2·2) minutes.     

Simultaneous infusions of propofol and ketamine in ponies premedicated with detomidine: a pharmacokinetic study

The pharmacokinetics of propofol and ketamine administered together by infusion were investigated in four ponies. Blood propofol and plasma ketamine and norketamine concentrations were measured by high performance liquid chromatography. After premedication with detomidine (20 μg kg⁻¹) anaesthesia was induced with ketamine (2·2 mg kg ⁻¹ intravenously). The trachea was intubated and the ponies were allowed to breathe 100 per cent oxygen. A bolus dose of propofol (0·5 mg kg⁻¹) was then administered intravenously and propofol and ketamine were infused for 60 and 45 minutes, respectively. The average mean infusion rate of propofol was 0·136 mg kg⁻¹ min⁻¹, and the ketamine infusion rate was maintained at 50 μg kg⁻¹ min⁻¹. The mean (SD) elimination half-lives of propofol and ketamine were 69·0 (8·0) and 89·8 (26·7) minutes, the mean volumes of distribution at steady state were 0·894 (0·161) litre kg⁻¹ and 1·432 (0·324) litre kg⁻¹ the mean body clearances were 33·1 (4·5) and 23·9 (3·8) ml kg⁻¹ min⁻¹ and the mean residence times for the infusion were 87·1 (4·1) and 110·7 (8·2) minutes, respectively. Norketamine, the main metabolite of ketamine, was detected throughout the sampling period. The mean residence time for norketamine was 144 (16) minutes. All the ponies recovered quickly from the anaesthesia; the mean times to sternal recumbency and standing were 11·1 (5·3) and 30·0 (20·8) minutes, respectively, from the end of the infusion.     

Penetration of amoxycillin into the respiratory tract tissues and secretions in pigs

The pharmacokinetic properties of amoxycillin, and its penetration into respiratory tract tissues (alveolar macrophages, bronchial secretions, bronchial mucosa, lung tissue and lymph nodes), were determined in 20 healthy female pigs weighing 29 to 55 kg, after a single intravenous dose of 8·6 mg kg ⁻¹ bodyweight. Following intravenous administration the plasma concentration-time curves were best described by a three-compartment open model. The elimination half-life and the mean residence time were 2·5 and 1.4 hours, respectively. The volume of distribution at steady state was 0·52 litres kg ⁻¹, and the body clearance was 0·40 litres hour⁻¹ kg⁻¹. In all structures (except alveolar macrophages) amoxycillin concentration peaked at the first sampling point, one hour after drug administration. The tissue to plasma ratio (based on AUC values) were 0·33 for bronchial secretions, 0·37 for bronchial mucosa, 0·39 for lung tissue and 0·68 for lymph nodes. Traces of amoxycillin were found in alveolar macrophages, but the concentrations were below the limit of quantification. The concentration of amoxycillin in secretions and tissue decreased by a slower rate than the concentration in plasma, resulting in increasing secretion- and tissue-to-plasma concentration ratios.     

Kinetic disposition, systemic bioavailability and tissue distribution of apramycin in broiler chickens

Apramycin was administered to chickens orally, intramuscularly and intravenously to determine blood concentration, kinetic behaviour, bioavailability and tissue residues. Single doses of apramycin at the rate of 75 mg kg⁻¹ body weight were given to broiler chickens by intracrop, i.m. and i.v. routes. The highest serum concentrations of apramycin were reached 0·20 and 0·76 hours after the oral and i.m. doses with an absorption half-life () of 0·10 and 0·19 hours and an elimination half life () of 1·22 and 2·31 hours respectively. The systemic bioavailability was 2·0 and 58 per cent after intracrop and i.m. administration, respectively, indicating poor absorption of the drug when given orally.Following i.v. injection, the kinetics of apramycin was described by a two-compartment open model with a () of 1·5 hours, () of 2·1 hours, V_d(ss) (volume of distribution) of 4·82 litre kg⁻¹ and C1_(B) (total body clearance) of 1·88 litre kg⁻¹ hour⁻¹. The serum protein-binding of apramycin was 26 per cent.The highest tissue concentrations of apramycin were present in the kidneys and liver. No apramycin residues were detected in tissues after six hours except in the liver and kidneys following intracrop dosing and kidneys following i.m. administration.     

Pharmacokinetics of oxytetracycline after intramuscular administration with lidocaine in sheep, comparison with a conventional formulation

The pharmacokinetic behaviour of oxytetracycline (OTC) was studied in 11 sheep after intravenous and intramuscular administration at a single dosage of 20 mg kg⁻¹ bodyweight. A conventional formulation was injected by the intravenous route and two different preparations were administered by the intramuscular route: a conventional formulation (T-100) and an aqueous solution of OTC with lidocaine (1 per cent) (OTC-Q. The objective was to determine whether there are differences between both formulations in the disposition kinetics of OTC after intramuscular administration to sheep. After intravenous administration of the conventional formulation, plasma oxytetracycline concentrations were best fitted to an open two-compartment model. Mean apparent volume of distribution was 0·77±0·02 litre kg⁻¹ and the harmonic mean half-life was three hours. The OTC transfer process between central and peripheral compartments was fast and that did not influence the elimination process. After intramuscular administrations of both formulations, half-lives were longer than after intravenous administration (mean values of 14·1 and 58·2 hours for T-100 and OTC-L respectively). In both cases, a biphasic absorption, a ‘flip-flop’ model and a complete bioavailability were found. OTC-L provided therapeutic plasma concentrations over 0·5 μg ml⁻¹ (the minimum inhibitory concentration for most susceptible pathogens) for a longer period of time than T-100 (72 hours compared with 36 or 48 hours).     

Suppression of ovarian oxytocin secretion after intra-luteal administration of the arachidonate 5-lipoxygenase inhibitor BWA4C in the ewe

The effect of an intra-luteal injection of the 5-lipoxygenase (5-LO) inhibitor BWA4C (2 mg in 50 μ1 dmso) on the secretion of oxytocin (OT) from the corpus luteum in response to a close-arterial infusion of prostaglandin (PG)-F_2α (5 ng mint) was examined in anaesthetised sheep. Within 30 minutes of administration both basal (pre-infusion) and PGF_2α stimulated OT release into the posterior vena cava were significantly (P<0·01) reduced. These results are consistent with the proposition that 5-LO products of arachidonic acid may modulate OT secretion from the ovine corpus luteum.     

Use of a pulsed electromagnetic field for treatment of post-operative pain in dogs: a pilot study

Objective To determine if pulsed electromagnetic field (PEMF) therapy reduces post‐operative pain in dogs following ovariohysterectomy, and to evaluate PEMF interaction with post‐operative morphine analgesia. Study design Randomized controlled clinical trail. Animals Sixteen healthy dogs weighing 18 (10–32) kg [median (range)] and aged 13 (3–36) months. Materials and methods Anesthesia consisted of atropine (0.04 mg kg^?1, SC), acepromazine (0.02 mg kg^?1, SC), fentanyl (0.01 mg kg^?1, SC), thiopental (10–15 mg kg^?1, IV) and halothane in oxygen. Ovariohysterectomies were performed by senior veterinary students. Pain score (numeric rating scale, 0–28), pulse rate, respiratory rate, indirect mean arterial pressure (MAP), and body temperature were evaluated prior to anesthetic premedication, at extubation, 30 minutes after extubation, and then hourly for 6 hours. Following extubation, dogs were randomly divided into four groups: a control group that received 0.9% NaCl, IV, and no PEMF; a magnet group that received 0.9% NaCl, IV, and PEMF; a morphine group that received morphine 0.25 mg kg^?1, IV, and no PEMF; and, a magnet/morphine group that received morphine 0.25 mg kg^?1, IV, and PEMF. A single observer, blinded to treatment, obtained all behavioral observations and physiologic data. Data were analyzed using the Kruskal–Wallis statistical test with a significance of p < 0.05. Results Significant differences in MAP (mm Hg) [median (range)] occurred at 300 minutes [morphine 108 (83–114) and magnet/morphine 90 (83–97) < magnet 135 (113–117)], and at 360 minutes [magnet/morphine 93 (81–100) < control 127 (111–129) and magnet 126 (111–129)]. At 30 minutes the total pain score for the magnet/morphine group [1.5 (0–5)] was significantly less than control [8 (6–13)], but not different from magnet [5.5 (4–7)] or morphine [4.5 (2–9)]. Conclusions and clinical relevance Although no clear benefit was seen in this study, the results suggest that PEMF may augment morphine analgesia following ovariohysterectomy in dogs, and that further study of the analgesic effects of PEMF is warranted.     

Recovery Quality After Romifidine Versus Detomidine Infusion During Isoflurane Anesthesia in Horses

To examine the influence of detomidine or romifidine on recovery quality from isoflurane anesthesia, 78 anesthetic records were reviewed, from horses that had received romifidine (group R) during premedication [80–120 μg kg⁻¹ IV], anesthetic maintenance (40 μg kg⁻¹ hour⁻¹ IV), and recovery (20 μg kg⁻¹ IV) or detomidine (group D), at doses of 10–20 μg kg⁻¹ IV, 5 μg kg⁻¹ hour⁻¹ IV, and 2.5 μg kg⁻¹ IV, respectively. Duration of the different recovery phases, the number of attempts to sternal and standing, scores for transition to standing (TrSta), balance and coordination once standing (BC), and final recovery score (FS) were compared between groups using a Mann–Whitney U-test, independent t-test, or chi-squared test, as appropriate (alpha 0.05). Parametric data are represented as the mean ± standard deviation, and nonparametric data as the median (interquartile range). Compared with group D (25 horses), horses in group R (53 horses) needed significantly fewer attempts to achieve sternal recumbency [R 1 (1–1) vs. D 1 (1–2)], remained significantly longer in sternal recumbency [R 10 (3–14,5) vs. D 5 (1–9,5) minutes], needed significantly less attempts to stand [R 1 (1–1) vs. D 2 (1–4)], and a significantly shorter time to stand after making their first attempt [R 0 (0–0) vs. D 3 (0–6) minutes], with significantly better scores for TrSta, BC, and FS in group R. The results suggest that, at the doses used, romifidine provides a better recovery quality.     

A comparison of edrophonium and neostigmine for the reversal of mivacurium-induced neuromuscular blockade in sheep

The rate of reversal of neuromuscular block was compared in 36 sheep receiving either edrophonium (500 μg kg⁻¹) and atropine (80 μg kg⁻¹), neostigmine (50 μg kg⁻¹) and atropine (80 μg kg⁻¹) or saline (10 ml), using the train of four count (TO4C) recorded at n. facialis - m. levator nasolabialis. Neuromuscular block was produced with mivacurium (200 μg kg⁻¹) followed later by a single incremental dose of 70 μg kg⁻¹. Antagonists or saline were given when spontaneous recovery from the incremental dose (T04C = 1) = 1 begun. The T04C increased from 1 to 4 in all animals, in all treatment groups within 10 minutes of reversal. The T04C was 4 in all animals five minutes after edrophonium, and seven minutes after neostigmine; differences were not statistically significant. The T04C was significantly higher with edrophonium two and three minutes after antagonism compared with saline. The data show that spontaneous recovery from mivacurium is rapid in sheep, although reversal is accelerated by anticholinesterase drugs.     

Blood lactate disappearance after maximal exercise in trained and detrained horses

The influence of training on blood lactate concentrations during treadmill exercise and a 40-minute inactive recovery period was examined in seven trained and seven detrained thorough-bred horses. Lactate concentrations were measured in venous blood collected at the end of each exercise state, and at intervals for 40 minutes afterwards. Measurements were made of maximum oxygen uptake (V̇O_2max, ml kg⁻¹ min⁻¹), VLA4 (velocity at which blood lactate concentration was 4 mmol litre⁻¹); LA8 (lactate concentration [mmol litre⁻¹] during exercise at 8 m sec⁻¹), peak lactate (highest lactate concentration after exercise), LA40 (lactate concentration 40 minutes after exercise), the time of peak lactate concentration (minutes after exercise) and the rate of disappearance of blood lactate (Rt_d). The trained horses had a significantly lower LA8 (2·1 ± 0·1 vs 6·5 ± 1 mmol litre⁻¹, P<0·01), higher VLA4 (9·8 ± 0·2 vs 5·8 ± 0·6 m sec⁻¹, P<0·01) and higher V̇0_2max (156·3 ± 3·8 vs 107·1 ± 3·9 ml kg⁻¹ min⁻¹, P<0·001). The value of Rt_d and the time of peak lactate concentration were not significantly different.     

Comparison between dexmedetomidine and acepromazine in combination with methadone for premedication in brachycephalic dogs undergoing surgery for brachycephalic obstructive airway syndrome

ObjectiveTo compare dexmedetomidine with acepromazine for premedication combined with methadone in dogs undergoing brachycephalic obstructive airway syndrome (BOAS) surgery.Study designRandomized, blinded clinical study.AnimalsA group of 40 dogs weighing mean (± standard deviation) 10.5 ± 6 kg, aged 2.6 ± 1.9 years.MethodsDogs received either acepromazine 20 μg kg^–1 (group A) or dexmedetomidine 2 μg kg^–1 (group D) intramuscularly with methadone 0.3 mg kg^–1. Anaesthesia was induced with propofol and maintained with sevoflurane. Sedation (0–18), induction (0–6) and recovery (0–5) qualities were scored. Propofol dose, hypotension incidence, mechanical ventilation requirement, extubation time, additional sedation, oxygen supplementation, regurgitation and emergency intubation following premedication or during recovery were recorded. Data were analysed using t tests, Mann-Whitney U or Chi-square tests.ResultsGroup A dogs were less sedated [median (range): 1.5 (0–12)] than group D [5 (1–18)] (p = 0.021) and required more propofol [3.5 (1–7) versus 2.4 (1–8) mg kg^–1; p = 0.018]. Induction scores [group A: 5 (4–5); group D 5 (3–5)] (p = 0.989), recovery scores [group A 5 (4–5); group D 5(3–5)](p = 0.738) and anaesthesia duration [group A:93 (50–170); group D 96 (54–263) minutes] (p = 0.758) were similar between groups. Time to extubation was longer in group A 12.5 (3-35) versus group D 5.5 (0–15) minutes; (p = 0.005). During recovery, two dogs required emergency intubation (p > 0.99) and five dogs required additional sedation (p > 0.99). Oxygen supplementation was required in 16 and 12 dogs in group A and D, respectively (p = 0.167); no dogs in group A and one dog in group D regurgitated (p = 0.311).Conclusions and clinical relevanceDexmedetomidine 2 μg kg^–1 produces more sedation but similar recovery quality to acepromazine 20 μg kg^–1 combined with methadone in dogs undergoing BOAS surgery.     

Influence of age of the donor sheep on the phagocytosis of Staphylococcus aureus subspecies anaerobius and S aureus by neutrophils

The age of the sheep donating neutrophils had a marked influence in vitro on their phagocytic ability with respect to Staphylococcus aureus and S aureus subspecies anaerobius. Neutrophils from lambs five to eight weeks old phagocytosed these organisms significantly less efficiently (P<0–001) than neutrophils from adults two to four years old. However, neutrophils from the young animals phagocytosed S aureus significantly (P<0·001) better than S aureus subspecies anaerobius (61·5 v 53·8 (per cent), whereas there was no significant difference in the ability of the neutrophils from adult sheep to phagocytose S aureus and S aureus subspecies anaerobius (68·2 v 68·2 per cent).     

Comparison of the neuromuscular blocking effects of cisatracurium during isoflurane or propofol anesthesia in dogs

ObjectiveTo compare the neuromuscular blocking effects of cisatracurium during isoflurane versus propofol anesthesia in dogs.Study designProspective, randomized study.AnimalsA total of 20 healthy, client-owned dogs (16 females, four males) weighing 12.5–22 kg and aged 1–8 years.MethodsDogs undergoing elective surgery were randomized in equal numbers to an isoflurane (ISO) or propofol (PPF) group. Other drugs used during anesthesia were equal between groups. Single-twitch (ST) stimulation was used to monitor neuromuscular response. After recording the baseline ST (T0), cumulative doses of cisatracurium (0.05 mg kg^–1) were administered intravenously until ST/T0 ≤5%. Effective doses 50 (ED₅₀) and 95 (ED₉₅) of cisatracurium in each group were calculated from group dose-response curves. Recovery of ST (TR) was defined as spontaneous recovery of ST to 80–120% of T0 remaining stable for 2 minutes. The ST after each dose of cisatracurium, duration 25% (time after the last dose until 25% recovery of TR), recovery index (time to recovery from 25% to 75% of TR) and duration to TR (time after the last dose until recovery of TR) were recorded.ResultsIncremental doses of cisatracurium, median (range), were 2 (1–3) in ISO and 4 (2–5) in PPF to achieve ≥95% depression of ST/T0 (p < 0.01). ED₅₀ and ED₉₅ were 20 μg kg^–1 and 117 μg kg^–1 in ISO and 128 μg kg^–1 and 167 μg kg^–1 in PPF, respectively. The duration 25%, recovery index and duration to TR, median (range), were longer in ISO [22.6 (10.3–24.3), 5.3 (3.0–7.8) and 36.1 (20.1–49.7) minutes, respectively] than in PPF [10.2 (6.8–16.5), 3.0 (2.0–3.8) and 17.7 (14.2–28.7) minutes, respectively] (p < 0.01).Conclusions and clinical relevanceCisatracurium-induced neuromuscular blockade was significantly enhanced and prolonged by isoflurane compared with propofol.     

The effect of neuraxial morphine on postoperative pain in dogs after extrahepatic portosystemic shunt attenuation

ObjectiveTo investigate the analgesic effect of epidural morphine after surgical extrahepatic portosystemic shunt (EHPSS) attenuation.Study designRandomized clinical trial.AnimalsA total of 20 dogs with a congenital EHPSS.MethodsDogs were randomly allocated to be given either a single epidural dose of 0.2 mg kg^–1 preservative-free morphine (group M) or not (group C) before surgery. All dogs were administered 0.3 mg kg^–1 methadone intravenously (IV) as preanaesthetic medication. Pain scores were determined every 2 hours for the first 24 hours postoperatively using the short-form Glasgow Composite Measure Pain Scale (GCMPS-SF). Dogs with a GCMPS-SF pain score >4/20 or >5/24 received 0.1 mg kg^–1 methadone IV as rescue analgesia and were reassessed 30 minutes later. If more than three doses of methadone were administered in a 2 hour period, alternative pain relief was provided and a treatment failure recorded. The GCMPS-SF pain scores and number of rescue analgesia injections were analysed over 24 hours. The last observation carried forward method was applied in case of treatment failure. Food consumption and time to first urination were recorded. Data were analysed using a Mann–Whitney U test and presented as median (minimum–maximum range), with significance set at p < 0.05.ResultsGroup M showed lower GCMPS-SF pain scores [15 (11–41) versus 31 (11–86); p = 0.023] and lower postoperative methadone requirements [0 (0–0.2) versus 0.25 (0–0.5) mg kg^–1; p = 0.029] than group C. There were three treatment failures in group C only. Food consumption and time to first urination did not differ between groups.Conclusions and clinical relevanceEpidural morphine reduced the requirement for postoperative analgesia in this study population.     

Impact of surgical preparatory rinses with isopropyl alcohol or water on perioperative body temperature in pediatric female dogs and cats

ObjectiveTo describe the effects of presurgical preparation with an isopropyl alcohol or water rinse on the perioperative rectal temperature (RT) of puppies and kittens.Study designRandomized clinical trial.AnimalsA total of 48 intact female mixed breed puppies and 43 intact female Domestic Short Hair kittens aged 8–18 weeks.MethodsAll animals were premedicated with intramuscular buprenorphine (0.02 mg kg^–1) and acepromazine (0.05 mg kg^–1). Anesthesia was induced with intravenous propofol (4 mg kg^–1 to effect) for puppies or ketamine (5 mg kg^–1) and midazolam (0.25 mg kg^–1) for kittens. RT was measured every minute for the first 15 minutes at the beginning of hair/fur removal, then every 5 minutes for 45 minutes (dogs) and 35 minutes (cats). All animals were prepared for surgery using a 1.6% chlorhexidine solution, then rinsed with either isopropyl alcohol (group CA) or water (group CW).ResultsMean RT difference between the groups was not significant at any time point. The mean RT at 45 minutes for dogs was 35.9 °C and 36.0 °C in groups CA and CW, respectively (p = 0.74). The mean RT at 35 minutes for cats was 35.1 °C in both groups (p = 0.84).Conclusions and clinical relevanceThe use of either water or alcohol as a rinsing agent results in the same degree of perioperative temperature change. Other factors that contribute to perioperative hypothermia should be considered when choosing between these rinsing agents in surgical preparation of pediatric and small animals.     

Pharmacokinetics and bioavailability of moxifloxacin in buffalo calves

The pharmacokinetics of moxifloxacin were investigated in buffalo calves following a single intravenous and intramuscular administration of moxifloxacin (5 mg kg⁻¹ body wt.). Moxifloxacin concentrations in plasma and urine were determined by microbiological assay. Pharmacokinetic analysis of disposition data indicated that intravenous administration data were best described by a two compartment open model, whereas intramuscular administration data were best described by a one compartment open model. Following intravenous administration, the elimination half life (t_1/2β), volume of distribution (Vd_(area)) and total body clearance were 2.69 ± 0.14 h, 1.43 ± 0.08 L kg⁻¹ and 371.2 ± 11.2 ml kg⁻¹ h⁻¹, respectively. Following intramuscular administration, the absorption half life (t_1/2ka) was 0.83 ± 0.20 h. The systemic bioavailability (F) of moxifloxacin in buffalo calves was 80.0 ± 4.08%. Urinary excretion of moxifloxacin was less than 14% after 24 h of administration of drug. In vitro binding of moxifloxacin to plasma proteins of buffalo calves was 28.4 ± 3.77%. From the data of surrogate markers (AUC/MIC, C_max/MIC), it was determined in the buffalo calves that when administered by intravenous or intramuscular route at 5 mg kg⁻¹, moxifloxacin is likely to be effective against bacterial isolates with MIC ? 0.1 μg ml⁻¹.     

The isoflurane sparing effect of a medetomidine constant rate infusion in horses

This clinical study analysed the anaesthetic sparing effect of a medetomidine constant rate infusion (CRI) during isoflurane anaesthesia in horses. Forty healthy horses undergoing different types of orthopaedic and soft tissue surgeries were studied in a randomized trial. Orthopaedic surgeries were primarily arthroscopies and splint bone extractions. Soft tissue surgeries were principally castrations with one ovariectomy. All horses received 0.03 mg kg^?1 acepromazine IM 1 hour prior to sedation. Group A (11 orthopaedic and nine soft tissue surgeries), was sedated with 1.1 mg kg^?1 xylazine IV, group B (13 orthopaedic and seven soft tissue surgeries) with 7 µg kg^?1 medetomidine IV. Anaesthesia was induced in both groups with 2.2 mg kg^?1 ketamine and diazepam 0.02 mg kg^?1 IV. Maintenance of anaesthesia was with isoflurane (ISO) in 100% oxygen, depth of anaesthesia was always adjusted by the first author. Group B received an additional CRI of 3.5 µg kg^?1 hour^?1 medetomidine. Respiratory rate (RR), heart rate (HR), mean arterial blood pressure (MAP), Fe ′ISO and Fe ′CO₂ were monitored with a methane insensitive monitor (Cardiocap 5, Ohmeda, Anandic, Diessenhofen) and noted every 5 minutes. Arterial blood was withdrawn for gas analysis (PaO₂, PaCO₂) 5 minutes after the induction of anaesthesia and every 30 minutes thereafter. Dobutamine (DOB) was given as a CRI to maintain mean arterial blood pressure above 70 mm Hg. Data were averaged over time (sum of measurements/number of measurements) and tested for differences between groups by unpaired t‐tests. There were no significant differences between the groups in terms of body mass (group A, 508 ± 73.7 kg; group B, 529.25 ± 78.4 kg) or duration of anaesthesia (group A, 125.5 ± 36 minutes; group B, 121.5 ± 48.4 minutes). The mean Fe ′ISO required to maintain a surgical plane of anaesthesia was significantly higher in group A (1.33 ± 0.13%) than in group B (1.07 ± 0.19%; p = 2.78 × 10^?5). Heart rate was different between the two groups (group A, 42.2 ± 8.3; group B, 32.6 ± 3.5; p = 8.8 × 10^?5). Dobutamine requirements were higher in group A (group A, 0.72 ± 0.24 μg kg^?1 minute^?1; group B, 0.53 ± 0.23 μg kg^?1 minute^?1; p = 0.023). Respiratory rate, Fe ′CO₂, PaO₂, PaCO₂ were not different between the groups. Adjustment of anaesthetic depth subjectively was easier with the medetomidine infusion and isoflurane (group B) than with isoflurane as a sole agent (group A). In group A 12 horses and in group B five horses showed purposeful movements on 27 (A) and 12 (B) occasions. They were given thiopental (group A, 0.0114 mg kg^?1 minute^?1; group B, 0.0023 mg kg^?1 minute^?1). In group A, a further 17 horses were given ketamine to deepen anaesthesia (52 occasions, 0.00426 mg kg^?1 minute^?1) whereas in group B only nine horses needed ketamine (34 occasions, 0.00179 mg kg^?1 minute^?1). An infusion of 3.5 µg kg^?1 MED during ISO anaesthesia resulted in a significantly reduced ISO requirement.     

A comparison of the haemodynamic effects of epidurally administered medetomidine and xylazine in dogs

Alpha₂ agonists have a significant role in epidural anaesthetic techniques. However, there are few reports regarding epidural administration of these drugs especially in small animals ( Greene et al. 1995; Keegan et al. 1995; Vesal et al. 1996 ). This study compared the haemodynamic effects of xylazine and medetomidine after epidural injection in dogs. Six dogs (four females and two males) weighing 27.5 ± 3.39 kg, aged 5.6 ± 1.42 years were studied on two separate occasions one month apart. Dogs were sedated with 0.5 mg kg^?1 diazepam IM and 0.1 mg kg^?1 acepromazine IM. After 20 minutes, a lumbosacral epidural injection of 0.25 mg kg^?1 xylazine was administered (group X). One month later, following the same sedation, 15 µg kg^?1 medetomidine was administered epidurally (group M). Haemodynamic variables (ECG and indirect blood pressure (Doppler)), respiratory rate and rectal temperature were recorded before (baseline) and then every 5 minutes after the epidural injection, up to 60 minutes. Differences between groups were compared by a paired t‐test. Within group changes were compared to basal values by anova . A p‐value of < 0.05 was considered statistically significant. Both groups showed significant reductions in heart rate (106.3 ± 7.7 beats minute^?1 baseline versus 67.7 ± 7.6 (group M); 91 ± 3.8 baseline versus 52.3 ± 9 (group X)) and mean arterial blood pressure (113.1 ± 12.3 mm Hg baseline versus 87 ± 11 (group M); 118 ± 7 baseline versus 91 ± 14 (group X)). There were no differences between groups in these variables. After epidural injection, first degree atrioventricular block was recorded significantly more often in group X (50% against 33%) but second degree block was significantly more frequent in group M (66% against 33%). Also 50% of dogs in group X and 66% in group M showed sinus arrest. Respiratory rate decreased significantly in both groups following the epidural injection (20.66 ± 0.66 minute^?1 baseline versus 16.33 ± 4.77 (group M); 37.66 ± 0.56 baseline versus 16.33 ± 1.81 group X), but no differences between groups were observed. Rectal temperature decreased significantly in group X (38.16 ± 0.21) with respect to the basal measurement (39.30 ± 0.14 °C). In group M, there was no significant reduction in temperature, however, no statistical difference in rectal temperature was found between groups. This study shows that 0.25 mg kg^?1 xylazine and 15 µg kg^?1 medetomidine produce similar, significant cardiovascular and respiratory changes following lumbosacral epidural administration in dogs.     

Heart Rate,Net Cost of Transport,and Metabolic Power in Horse Subjected to Different Physical Exercises

Considering that workload can also be expressed in terms of estimated net transport cost (COT), the metabolic energy needed to transport unit mass of animal unit distance, the aim of our study was to describe the heart rate (HR), COT, and the total metabolic power requirement per kilogram (P) during different exercises (aerobic, anaerobic, and aerobic–anaerobic exercises). On the basis of their attitude, 25 horses, divided into five equal groups, traveled a distance of 6,000 m, walking at 100 m/min in a horse walker (group A); performed 20-minute treadmill walk at 130 m/min, average speed up gradient of 5% (group B); performed a 700-m-long show jumping course with 13 fences (group C); traveled a distance of 2,100 m galloping at a speed of 700 m/min (group D); and traveled a distance of 2,000 m trotting at a speed of 660 m/min (group E). On each horse, HR was continuously recorded by means of an equine HR monitor. COT was calculated with the following formula: (HR − 35) kg⁻¹ m⁻¹ 10³; P was calculated applying the formula: (HR − 35) min⁻¹ kg⁻¹. COT and P values, estimated from the mean HR, measured continuously during each experimental condition showed no linear relationship with HR and speed. The use of combined weight of horse and tack (group C and D) and horse, tack, and sulky (group E) statistically changed the results of formula application. COT and P change in different exercises and provide additional information about performance in athletic horses.     

Inhibition of acetylcholinesterase activity by rivastigmine decreases lipopolysaccharide-induced IL-1β expression in the hypothalamus of ewes

The present study was designed to determine the effect of subcutaneous rivastigmine treatment on IL-1β expression and IL-1 type I receptor (IL-1R1) gene expression in the hypothalamic structures (preoptic area [POA], anterior hypothalamus [AHA], and medial basal hypothalamus [MBH]) of ewes after lipopolysaccharide (LPS) treatment. Endotoxin treatment increased (P ≤ 0.01) both IL-1β and IL-1R1 gene expression in the POA, AHA, and MBH compared with the control group, whereas concomitant rivastigmine and LPS injection abolished this stimulatory effect. It was also found that LPS elevated (P ≤ 0.01) IL-1β concentration in the hypothalamus (71.0 ± 2.3 pg/mg) compared with controls (16.1 ± 3.6 pg/mg). The simultaneous injection of LPS and rivastigmine did not increase IL-1β concentration in the hypothalamus (24.6 ± 13.0 pg/mg). This central change in IL-1β synthesis seems to be an effect of acetylcholinesterase (AChE) inhibition by rivastigmine, which decreases (P ≤ 0.01) the activity of this enzyme from 78.5 ± 15.0 μmol · min⁻¹ · g⁻¹ of total protein in the control and 68.8 ± 9.8 μmol · min⁻¹ · g⁻¹ of total protein in LPS-treated animals to 45.2 ± 5.6 μmol · min⁻¹ · g⁻¹ of total protein in the rivastigmine and LPS-treated group. Our study showed that rivastigmine could effectively reverse the stimulatory effect of immune stress induced by LPS injection on IL-1β synthesis through a decrease in AChE activity in the hypothalamic area of sheep. Our results also proved that the cholinergic anti-inflammatory pathway could directly modulate the central response to endotoxin.